Cryptopleurine analogs with modification of e ring exhibit different mechanism to rac-cryptopleurine and tylophorine.

Abstract

Tylophorine analogs exhibit a broad range of pharmacological activities, including anti-cancer, anti-inflammatory, anti-autoimmune, and anti-virus effects. Structure-activity relationship study of different structure tylophorine analogs can provide further understanding of their biological activity. Modifications on the E ring of the quinolizidine moiety of cryptopleurine analogs changed the potency and the selective inhibitory effect on NF-κB, AP-1, and CRE signaling pathways. Functional cryptopleurine analogs showed potent inhibition of NF-κB signaling pathway in both HepG2 and HEK-293 cell lines. The E ring structure analogs also differed in suppression of protein translation, and expression of cyclin D1. Our results showed that DCB-3503 or Rac-cryptopleurine could be a scaffold for modification to yield compounds with different mechanisms of action.

• Authors: Ying Wang, Hui-Chyn Wong, Elizabeth A Gullen, Wing Lam, Xiaoming Yang, Qian Shi, Kuo-Hsiung Lee, Yung-Chi Cheng
• Journal: PloS one (PLoS One) Vol. 7 Issue 12 Pg. e51138 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 23251437 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Alkaloids
• Cyclic AMP Response Element-Binding Protein
• Indolizines
• NF-kappa B
• Phenanthrenes
• Transcription Factor AP-1
• cryptopleurine
• tylophorine

Topics

• Alkaloids (pharmacology)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• Indolizines (pharmacology)
• NF-kappa B (metabolism)
• Phenanthrenes (pharmacology)
• Signal Transduction
• Transcription Factor AP-1 (metabolism)